This study was an investigation of arterial contractility in response to high-intensity focused ultrasound (HIFU) and of histologic changes to the artery with various intensities of HIFU. We constructed a prototype HIFU transducer in combination with an imaging probe that provides color Doppler imaging and Doppler velocimetry. HIFU was applied through the skin to deep femoral arteries in left thighs of Sprague-Dawley rats; color images of the blood flow were used to aim the HIFU beam. Peak intensities used were 530, 1080, 2750 and 4300 W/cm2. The duration of each HIFU exposure was 5 s. HIFU was applied to five focal spots of each leg. These focal spots were aligned with a spacing of 1.0 mm so as to form a line across the artery. Blood flow occlusion was accomplished by HIFU at an intensity of 4300 W/cm2, but the flow continued with the lower intensities. Peak systolic velocities (PSVs) of blood flow as measured by Doppler velocimetry increased in the arteries to which HIFU had been applied at 1080 and 2750 W/cm2. The increase corresponded with HIFU intensity. Exposure to HIFU at 530 W/cm2 did not change the blood flow velocity. Histologic studies have demonstrated that exposure to HIFU at 2750 and 4300 W/cm2 leads to vacuolar degeneration and destruction of elastic fibers of the tunica media of the artery. Exposure at 1080 W/cm2 led to increased PSV, but did not induce histologic changes in the vessel wall. In conclusion, the response of the artery to HIFU varied with intensity. Vascular contraction without tissue degeneration occurred at low intensity; with increasing intensity, the tissue degeneration detectable in histology reduced the vascular diameter and, finally, at high intensity, the blood flow was occluded. Although these phenomena appeared to be mainly due to thermal effects, mechanical effects might have some role, particularly on vascular contraction.